JP2518692B2 - Muscle maintenance agent, nutrient tonic, infusion agent, nutritional supplement, fatigue recovery agent and lactic acid production regulator - Google Patents

Description

The present invention acts on the muscular and nervous systems containing a composition composed of amino acids contained in the saliva secreted by the hornet (Vespa) larvae. It relates to a composition.

(Prior Art and Problems to be Solved by the Invention) Heretofore, there have been almost no reports on wasp larvae, particularly on saliva secreted by the larvae, and their composition has not been elucidated at all. It was also completely unclear what nutrition contributed to the muscular sustainability of the hornet.

The present inventor has studied saliva secreted by various hornet larvae, clarified its composition, and found that the composition acts as an extremely effective muscle-strengthening agent. I came.

Accordingly, an object of the present invention is to provide an amino acid composition having a fatigue recovery action, a nerve action, and a lactic acid production regulating action based on muscle continuity.

(Means for Solving the Problems) As a result of intensive studies on the composition of the composition contained in the saliva secreted by various hornet larvae, the present inventor has found that the composition is a normal protein or its hydrolyzate. It has been found that the composition contains almost no aspartic acid or glutamic acid, which is contained in a relatively large amount in a product, and is an amino acid composition mainly containing proline and glycine.

In addition, they have found that this composition is effective in reducing fatigue and maintaining exercise by lowering blood lactic acid levels, and have completed the present invention.

That is, the present invention relates to an amino acid composition comprising 2 to 15 mol of threonine, 4 to 30 mol of proline, 7 to 20 mol of glycine, 4 to 8 mol of valine, and 3 to 8 mol of isoleucine.
-9 mol, leucine 2-12 mol, tyrosine 1-9 mol, phenylalanine 0.5-5 mol, lysine 5-11 mol
It is an object of the present invention to provide a composition characterized in that it contains methionine, tryptophan, histidine, and arginine in a proportion of 5 mol or less, respectively.

Similarly, the present invention provides a fatigue recovery agent containing the above composition,
The present invention relates to a lactic acid production regulator and a nerve agent.

The composition of the present invention has been clarified by analyzing the amino acids contained in various wasp larval saliva with an amino acid analyzer and completed as an amino acid composition containing the active ingredients.

 Examples of compositions of the present invention are shown in Table 1 below.

In the table, the yellow-tailed hornet (Vespa xanthopter)
a) Derived composition, Mon is a wasp (Vespa crabr)
o) A composition derived from the Japanese hornet (Vespa tropi)
ca) -derived composition, the stag beetle is Vespa
analis) -derived composition, giant wasp (Vespa)
1 shows a composition from C. mandarinia).

It is particularly preferable to use an L-amino acid as an amino acid constituting the composition.

The composition of the present invention comprises 2 to 15 mol of threonine (Thr), 4 to 30 mol of proline (Pro), 7 to 20 mol of glycine (Gly), 4 to 8 mol of valine (Val), and isoleucine (I). -Leu) 3 to 9 mol, leucine (Leu) 2 to 12
Mol, 1 to 9 mol of tyrosine (Tyr), 0.5 to 5 mol of phenylalanine (Phe), 5 to 11 mol of lysine (Lys), and methionine (Met) in a proportion of 5 mol or less, Contains tryptophan (Trp), histidine (His), and arginine (Arg).

In addition, 3 moles or less of taurine (Tau), 2 moles or less of ethanolamine phosphate (P-EtAm),
1 mol or less of aspartic acid (Asp), 5 mol or less of serine (Ser), 5 mol or less of asparagine (Asp), 4 mol or less of glutamic acid (Gl
u), 12 mol or less of alanine (Ala), 0.5 mol or less of cysteine (Cys), 1 mol or less of β
Alanine (β-Ala), 0.5 mol or less of γ-aminobutyric acid (GABA), 3 mol or less of ethanolamino (EtAm), 2 mol or less of ammonia (NH ₃ ), 3 mol or less,
It can contain up to 1 mole of ornithine (Orn), up to 1 mole of 1-methylhistidine (1-MeHis), up to 1 mole of 3-methylhistidine (3-MeHis).

For example, when the amino acid composition of the present invention is described based on the wasp-derived amino acid composition shown in Table 1, 6.5 mol of threonine, 17.1 mol of proline, and 18.2 mol of glycine
Mol, valine 5.6 mol, isoleucine 4.3 mol, leucine 5.8 mol, tyrosine 5.7 mol, phenylalanine 3.7 mol, lysine 8.2 mol, methionine 0.5 mol,
Composition A containing 2.1 mol of tryptophan, 2.5 mol of histidine and 3.3 mol of arginine, and the above composition A
Composition B containing 0.2 mol of aspartic acid, 2.4 mol of serine, 3.0 mol of glutamic acid, and 5.7 mol of alanine, and 0.5 mol of taurine, 0.2 mol of β-alanine, and γ-amino Composition C containing 0.3 mol of butyric acid, 1.0 mol of ethanolamino, 1.1 mol of ammonia, 1.0 mol of ornithine, 0.4 mol of 1-methylhistidine and 0.5 mol of 3-methylhistidine was used as the composition of the present invention. This can be exemplified as one embodiment.

In producing the composition of the present invention, the above-mentioned commercially available amino acids may be mixed at the above-mentioned predetermined ratio. Usually, the composition may be prepared by uniformly mixing in powder form, but the components may be dissolved in distilled water or mixed in a solution state, and then dried to produce the composition. The composition of the present invention is preferably manufactured at room temperature or lower.

The composition of the present invention exhibits a slight bitterness and suppresses the production of lactic acid during exercise. It is also useful for reducing fatigue and maintaining exercise by lowering blood lactic acid levels.

The composition of the present invention shows no toxicity even at 20 g / kg when administered orally to mice, and the LD ₅₀ is far higher than 20 g / kg.

The composition of the present invention is useful as a lactic acid production regulator, a blood lactate lowering agent, a fatigue recovery agent, and a muscle exercise continuation agent for humans and exercise. It is also useful as a nerve agent. Although the administration form is not particularly limited, oral administration, rectal administration, injection,
It can be by a general route such as administration by infusion. In the case of oral administration, the composition itself or a mixture with a pharmaceutically acceptable carrier, excipient, diluent, etc., is used as a powder, granule, tablet, capsule, troche, syrup, etc. Is also good. However, solid powders and tablets may take a long time to be absorbed, so that oral administration of the composition itself is preferred. In that case, it is preferable to administer as an aqueous solution together with a suitable additive such as salts such as sodium chloride, a pH adjuster, a chelating agent and the like. Other amino acids, aqueous vitamins, acids such as citric acid may be added to the composition of the present invention, and drinks (for example, soft drinks, powdered drinks, nutritional tonics, nutritional supplements) may be added with an appropriate flavor. Drink as a drug for the purpose). The injection may be prepared by adding an appropriate buffer, isotonic agent or the like and dissolving it in sterile distilled water.

Since the composition of the present invention has extremely low toxicity, the dose can be set in a very wide range. Further, it varies depending on the administration method and purpose of use, but is usually 0.5 to 5 g at a time, preferably 1 to 2 g at a time, 1 to 20 g, preferably 4 to 1 as a daily dose
It is preferably 0 g. When these solutions are used, 0.5 to 10% by weight of a solution is used in an amount of 10 to 1000 ml, preferably 1 to 4%.
The single dose may be 100 to 400 ml as a wt% solution.

Example 1 A 16 mg / ml aqueous solution (1.6 wt%) was prepared by dissolving composition B (VAAM) of the present invention having the composition of wasp in Table 1 at room temperature by adding component amino acids to distilled water at room temperature.

With respect to the VAAM aqueous solution, nutritional and biochemical tests will be used to explain the effect of increasing exercise duration, the effect of regulating lactic acid production, and the effect of lowering blood lactate.

Example 1. Nutritional test (1) Forced swimming test-1 A. Test method Five ddy male mice (19-20 g) of 5 weeks old were grouped into 5 mice.
Create a flow rate of 4-8m / min in a water tank with a diameter of 32cm and a depth of 30cm,
Forced swimming was performed, and the limit swimming time was measured.

B. Test results a) Change in critical swimming time with change in dose The VAAM aqueous solution of the present invention was used for 12.5, 25, 3
7.5 and 50μ were orally administered and swimming started 60 minutes later. As shown in Fig. 1, the limit swimming time was 10
It increased significantly from 0 min to 25 μ and 37.5 μ at 130 min. However, 50 μ showed a decrease. This is because the excess of body fluid accompanying the increase in the dose adversely affected swimming.

b) Effect of swimming start time after administration on marginal swimming time 25 μm, which is the optimal amount of solution obtained from the results of experiment a)
Swim start time from 0 minutes after oral administration of / g VAAM aqueous solution
Swim at 40 ° C for 180 minutes. 30 minutes after administration, a maximum swimming time of 170 minutes was obtained (FIG. 2). This was significantly longer than the casein / amino acid composition of the same concentration (CAAM, Table 2), and was longer than the control in the water administration group at all administration times.

From FIG. 2, it is clear that the 1.6 wt% VAAM aqueous solution of the present invention has a superior effect on exercise continuity over CAAM (casein amino acid composition).

c) Change in marginal swimming time due to change in water temperature Next, the water temperature in the swimming tank was changed from 25 ° C to 45 ° C every 5 ° C under the conditions of a dose of 25μ / g and a swimming start time of 60 minutes after administration. Measured the maximum swimming time at 35 ° C
Obtained the longest swimming time of 255 minutes. This was significantly different from the control (FIG. 3).

d) Change in the limit swimming time according to the age of the mouse The swimming time of 4, 5, 8, and 10-week-old mice was measured at a water temperature of 40 ° C. and a swimming start time of 60 minutes with the dose of the VAAM aqueous solution being 25 μ / g. At the age of 5 weeks, a critical swimming time of 180 minutes was obtained which was significantly different from the control group (FIG. 4).

e) Effect of the amino acid mixture on swimming time Using 5-week-old mice (15 hours before administration, 15 hours before administration), water was added to the control at a water temperature of 35 ° C., and a 10% glucose solution, a CAAM solution,
Then, the VAAM solution of the present invention was administered at 37.5 μ / g each,
Swimming started 30 minutes after administration. The control's limit swimming time was 154 minutes. CAAM was 190 minutes, 10% glucose was 157 minutes, and VAAM was 218 minutes (Figure 5).
This is because the 16% VAAM solution of the present invention has a CAAM
Solution and 10% dextrose solution.

2. Biochemical test Lactate test in blood and body tissue A. Test method One molecule of NADH produced when lactate was converted to pyruvate by lactate dehydrogenase was determined by absorption measurement at 340 nm. The test was performed using Sigma clinical reagents.

a) Influence of the composition of the present invention on blood lactate before and after swimming A 5-week-old mouse was orally administered with a 37.5 μg / g VAAM aqueous solution, and after 30 minutes a 0.3 g load was applied to start swimming. . Blood lactate was measured 30 minutes after administration before swimming and 30 minutes after swimming. Controls that administered distilled water before swimming, CAAM and VA
There was a difference with AM. Control 11.0 after swimming
mg / dl, CAAM was 12.3 mg / dl, VAAM was 9.21 mg / dl
And a significant difference was maintained. The 10% glucose solution showed high values before and after swimming. Even in this case, it was found that the combined use of VAAM suppressed the increase in lactic acid level (6th
Figure). Therefore, it is clear that the composition of the present invention works to suppress the increase in lactic acid level due to forced exercise.

b) Influence of the composition of the present invention on the lactate level in the muscle after swimming A 57.5-week-old mouse was orally administered with a 37.5 μg / g VAAM aqueous solution, and after 30 minutes, a 0.3 g load was applied to swim. Started.
Thirty minutes after swimming, the muscles of the hind legs were excised and lactic acid levels were measured. Before swimming, no difference was seen with any of the compositions. Lactate value in muscle after swimming was 0.381 mg / g muscle weight for control and 0.389 mg / g muscle weight for CAAM, but 0.366 mg for VAAM
/ g was significantly reduced. The 10% glucose solution showed high values (Table 3).

Therefore, it is shown that the composition of the present invention works to suppress the production of lactic acid in muscle by forced exercise.

[Brief description of the drawings]

FIG. 1 shows the change in the limit swimming time with the change in the dose of the composition of the present invention, and FIG. 2 shows the effect of the swimming start time on the swimming time after the administration of the composition of the present invention. , Third
The figure shows the change in swimming time with the change in water temperature, FIG. 4 shows the change in swimming time due to mouse age, FIG. 5 shows the effect of the amino acid mixture on the limit swimming time, and FIG. 6 shows the present invention. 2 shows the effect of the composition of Example 1 on blood lactate levels before and after swimming.

──────────────────────────────────────────────────続 き Continuation of the front page (51) Int.Cl. ⁶ Identification code Agency reference number FI Technical display location // A23L 1/305 A61K 37/18 ADD (72) Inventor Yoshizo Takiguchi Otemachi, Chiyoda-ku, Tokyo 2-6-3 Nippon Steel Corporation (56) References US Patent 4,780,475 (US, A) US Patent 5,026,721 (US, A)

Claims (6)

(57) [Claims] (1) Threonine is 2 to 15 mol, and proline is 4 to 4 mol.
30 mol, glycine 7-20 mol, valine 4-8 mol,
3 to 9 mol of isoleucine, 2 to 12 mol of leucine, 1 to 9 mol of tyrosine, 0.5 to 5 mol of phenylalanine, 5 to 11 mol of lysine, and methionine in a proportion of 5 mol or less, Tryptophan, histidine, muscle strength sustaining agent containing an amino acid composition containing arginine as an active ingredient, a nutritional tonic, an infusion agent, a nutritional supplement,
Fatigue recovery agent or lactic acid production regulator. 2. The muscle-strengthening agent according to claim 1, wherein the amino acid composition further contains aspartic acid in a proportion of 1 mol or less, serine in a proportion of 5 mol or less, glutamic acid in a proportion of 4 mol or less, and alanine in a proportion of 12 mol or less. Tonic, infusion solution, nutritional supplement, fatigue recovery agent or lactic acid production regulator. 3. The amino acid composition further comprises 3 mol or less of taurine, 1 mol or less of β-alanine and 0.1 mol of γ-aminobutyric acid.
The composition according to claim 2, which contains 5 mol or less, 3 mol or less of ethanolamine, 2 mol or less of ammonia, 3 mol or less of ornithine, 1 mol or less of 1-methylhistidine, and 1 mol or less of 3-methylhistidine. Muscular strength maintainer, nutritional tonic, nutritional supplement, infusion agent, fatigue recovery agent or lactic acid production regulator. 4. An amino acid composition comprising threonine 6.5 mol, proline 17.1 mol, glycine 18.2 mol, and valine 5.6 mol.
Mol, isoleucine 4.3 mol, leucine 5.8 mol, tyrosine 5.7 mol, phenylalanine 3.7 mol, lysine 8.2 mol, methionine 0.5 mol, tryptophan 2.
The muscle strength sustaining agent, nourishing tonic, infusion agent, nutritional supplement, fatigue relieving agent or lactic acid production regulator according to claim 1, which comprises 1 mol, 2.5 mol of histidine and 3.3 mol of arginine. 5. The amino acid composition further comprises aspartic acid.
0.2 mol, serine 2.4 mol, glutamic acid 3.0 mol,
The muscle strength sustaining agent, nutritional tonic, infusion agent, nutritional supplement, fatigue recovery agent or lactic acid production regulator according to claim (4), containing alanine in a ratio of 5.7 mol. 6. The amino acid composition further comprises taurine.
0.5 mol, 0.2 mol of β-alanine, and 0.1 mol of γ-aminobutyric acid.
3 mol, ethanolamine 1.0 mol, ammonia 1.1
Mole, ornithine 1.0 mole, 1-methylhistidine
The muscle-strengthening agent, nutritional tonic, infusion agent, nutritional supplement, fatigue recovery agent or lactic acid production regulator according to claim (5), comprising 0.4 mol and 0.5 mol of 3-methylhistidine.